Principal Investigator

Recent studies show that chronic SSRI treatment induces novel effects such as increase of the exitability of mature granule cells and expression of dopamine D1 receptors in the dentate gyrus (DG), called dematuration. Here, we investigated the role of PDEs in antidepressant effects, because inhibition of PDE results in increase of D1 receptor signaling. In this study, we revealed that PDE2 and PDE4 modulate the level of D1 receptor signaling in the DG. Combined treatment with fluoxetine and PDE2 and/or PDE4 inhibitors significantly enhanced D1 signaling induced by fluoxetine. These biochemical actions of PDE2 and PDE4 inhibitors may contribute to the development of new antidepressants.